Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Diagnostic performance of pressure-bounded coronary flow reserve.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Diagnostic performance of angiography-derived fractional flow reserve and CT-derived fractional flow reserve: A systematic review and Bayesian network meta-analysis.

OBJECTIVE: Accumulating evidence has demonstrated that fractional flow reserves (FFRs) derived from invasive coronary angiograms (CA-FFRs) and coronary computed tomography angiography-derived FFRs (CT-FFRs) are promising alternatives to wire-based FFRs. However, it remains unclear which method has better diagnostic performance. This systematic review and meta-analysis aimed to compare the diagnostic performances of the two approaches. METHODS: The Cochrane Library, PubMed, Embase, Medline (Ovid), the Chinese China National Knowledge Infrastructure Database (CNKI), VIP, and WanFang Data databases were searched for relevant studies that included comparisons between CA-FFR and CT-FFR, from their respective database inceptions until January 1, 2023. Studies where both noninvasive FFR (including CA-FFR and CT-FFR) and invasive FFR (as a reference standard) were performed for the diagnosis of ischemic coronary artery disease and were designed as prospective, paired diagnostic studies, were pulled. The diagnostic test accuracy method and Bayesian hierarchical summary receiver operating characteristic (ROC) model for network meta-analysis (NMA) of diagnostic tests (HSROC-NMADT) were both used to perform a meta-analysis on the data. RESULTS: Twenty-six studies were included in this NMA. The results from both the diagnostic test accuracy and HSROC-NMADT methods revealed that the diagnostic accuracy of CA-FFR was higher than that of CT-FFR, in terms of sensitivity (Se; 0.86 vs. 0.84), specificity (Sp; 0.90 vs. 0.78), positive predictive value (PPV; 0.83 vs. 0.70), and negative predictive value (NPV; 0.91 vs. 0.89) for the detection of myocardial ischemia. A cumulative ranking curve analysis indicated that CA-FFR had a higher diagnostic accuracy than CT-FFR in the context of this study, with a higher area under the ROC curve (AUC; 0.94 vs. 0.87). CONCLUSIONS: Although both of these two commonly used virtual FFR methods showed high levels of diagnostic accuracy, we demonstrated that CA-FFR had a better Se, Sp, PPV, NPV, and AUC than CT-FFR. However, this study provided only indirect comparisions; therefore, larger studies are warranted to directly compare the diagnostic performances of these two approaches.

Non-invasive fractional flow reserve estimation using deep learning on intermediate left anterior descending coronary artery lesion angiography images.

This study aimed to design an end-to-end deep learning model for estimating the value of fractional flow reserve (FFR) using angiography images to classify left anterior descending (LAD) branch angiography images with average stenosis between 50 and 70% into two categories: FFR > 80 and FFR ≤ 80. In this study 3625 images were extracted from 41 patients' angiography films. Nine pre-trained convolutional neural networks (CNN), including DenseNet121, InceptionResNetV2, VGG16, VGG19, ResNet50V2, Xception, MobileNetV3Large, DenseNet201, and DenseNet169, were used to extract the features of images. DenseNet169 indicated higher performance compared to other networks. AUC, Accuracy, Sensitivity, Specificity, Precision, and F1-score of the proposed DenseNet169 network were 0.81, 0.81, 0.86, 0.75, 0.82, and 0.84, respectively. The deep learning-based method proposed in this study can non-invasively and consistently estimate FFR from angiographic images, offering significant clinical potential for diagnosing and treating coronary artery disease by combining anatomical and physiological parameters.

Diagnostic Performance of Diastolic Hyperemia-Free Ratio Compared With Invasive Fractional Flow Reserve for Evaluation of Coronary Artery Disease.

Hyperemic and nonhyperemic pressure ratios are frequently used to assess the hemodynamic significance of coronary artery disease and to guide the need for myocardial revascularization. However, there are limited data on the diagnostic performance of the diastolic hyperemia-free ratio (DFR). We evaluated the diagnostic performance of the DFR compared with invasive fractional flow reserve (FFR). We performed a prospective, single-center study of 308 patients (343 lesions) who underwent DFR and FFR for evaluation of visually estimated 40% to 90% stenoses. Diagnostic performance of the DFR compared with FFR was evaluated using linear regression, Bland-Altman analysis, and receiver operating characteristic curves. The overall diagnostic accuracy of the DFR was 83%; the accuracy rates were 86%, 40%, and 95% when the DFR was <0.86, 0.88 to 0.90, and >0.93, respectively. The sensitivity, specificity, positive predicative value, and negative predictive value were 60%, 91%, 71%, and 87%, respectively. The Pearson correlation coefficient was 0.75 (p <0.05). The Bland-Altman analysis showed a mean difference of 0.09, and the area under the receiver operating characteristic curve was 0.88 (95% confidence interval 0.84 to 0.92, p <0.05). In conclusion, the DFR has a good diagnostic performance compared with FFR but 17% of the measurements were discordant. The diagnostic accuracy of the DFR was only 40% when the DFR was 0.88 to 0.90, suggesting that FFR may be useful in these arteries.

Electrocardiograms Do Not Detect Myocardial Ischemia in Patients With Williams Syndrome and Nonsyndromic Elastin Arteriopathy With Coronary Artery Stenosis.

Coronary artery stenosis (CAS) may affect up to 27% of patients with Williams syndrome (WS), which may lead to myocardial ischemia. Patients with WS face a 25- to 100-fold greater risk of sudden cardiac death, frequently linked to anesthesia. Assessing CAS requires either imaging while under general anesthesia or intraoperative assessment, with the latter considered the gold standard. Our study aimed to identify electrocardiogram (ECG) markers of myocardial ischemia in patients with WS or nonsyndromic elastin arteriopathy and documented CAS. We retrospectively reviewed patients with WS/elastin arteriopathy who underwent supravalvar aortic stenosis surgery and CAS assessment from January 1, 2006 to April 30, 2021. A pediatric electrophysiologist, not aware of the patients' CAS status, reviewed their preoperative ECGs for markers of ischemia. We assessed associations of study parameters using Wilcoxon rank-sum and Fisher's exact tests. Of 34 patients, 62% were male, with a median age of 20 months (interquartile range: 8 to 34). CAS was present in 62% (21 of 34), 76% of whom (16 of 21) were male. There were no ECG indicators of myocardial ischemia in patients with CAS. In conclusion, CAS was present in >1/2 the children with WS/elastin arteriopathy who underwent repair of supravalvar aortic stenosis. CAS in WS/nonsyndromic elastin arteriopathy does not appear to exhibit typical ECG-detectable myocardial ischemia. ECGs are not a useful screening tool for CAS in WS/elastin arteriopathy. Given the high anesthesia-related cardiac arrest risk, other noninvasive indicators of CAS are needed.

Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study.

INTRODUCTION AND OBJECTIVES: A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a "coarse-to-fine subpixel" algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. METHODS: This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a "coarse-to-fine subpixel" algorithm for lumen contour. RESULTS: Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and "gray zone" lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). CONCLUSIONS: CT-FFR with a new "coarse-to-fine subpixel" algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, "gray zone" lesions, and severely calcified lesions. Clinical Trial Register: NCT04731285.

The differences between patients with nonalcoholic fatty liver disease (NAFLD) and those without NAFLD, as well as predictors of functional coronary artery ischemia in patients with NAFLD.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with metabolic syndrome. It is the most common cause of cryptogenic cirrhosis. The disease is also involved in the occurrence and development of type 2 diabetes and atherosclerosis and can directly affect the outcome of patients with coronary heart disease. Therefore, the focus of treatment of nonalcoholic fatty liver disease has also begun to focus on the treatment of risk factors for atherosclerotic heart disease. In this study, we investigated the difference between patients with coronary artery stenosis combined with NAFLD and those without NAFLD and evaluated the predictive factors and value of functional coronary artery ischemia in patients with NAFLD. HYPOTHESIS: Many clinical factors (such as age, BMI, hyperglycemia) and imaging parameters (such as CACS grade) in the NAFLD group were different from those in the non-NAFLD group. The predictive model combined with multiple influencing factors has a good value in predicting coronary artery ischemia in patients with NAFLD. METHODS: We collected the clinical and imaging data of patients who underwent coronary computed tomography angiography and coronary artery calcification score (CACS) scans between January and June 2023. A total of 392 patients were included and divided into the NAFLD group and the non-NAFLD group. Based on CT fractional flow reserve (CT-FFR), patients with NAFLD were divided into CT-FFR ≤ 0.08 group and CT-FFR > 0.08 group. RESULTS: Significant differences were observed between the non-NAFLD and NAFLD groups in terms of age, body mass index, hyperglycemia, hyperlipidemia, triglyceride, high-density lipoprotein, coronary artery disease-reporting and data system (CAD-RADS) classification, CACS classification, number of diseased coronary arteries, and CT-FFR ≤ 0.80 ratio (p < .05). The CAD-RADS and CACS classifications can independently predict functional coronary artery ischemia in NAFLD patients. The combined use of CAD-RADS and CACS classifications resulted in an area under the curve of 0.819 (95% confidence interval: 0.761-0.876) for predicting coronary artery ischemia in NAFLD patients, which was higher than the individual classification methods (CAD-RADS: 0.762, CACS: 0.742) (p = .000). CONCLUSIONS: There are differences between patients with coronary artery stenosis and NAFLD and those without NAFLD. The CAD-RADS classification and CACS classification can economically and efficiently predict functional coronary artery ischemia in patients with NAFLD, which has crucial value in clinical diagnosis and treatment.

Graph-guided Gaussian Process-based Diagnosis of CVD Severity with Uncertainty Measures.

The severity of coronary artery disease can be assessed invasively using the Fractional Flow Reserve (FFR) index which is a useful diagnostic tool for the clinicians to select the treatment approach. The present work capitalizes a Gaussian process (GP) framework over graphs for the prediction of FFR index using only non-invasive imaging and clinical features. More specifically, taking the per-node one-hop connectivity vector as input, we employed a regression-based task by applying an ensemble of graph-adapted Gaussian process experts, with a data-adaptive fashion via online training. The main novelty of the work lies in the fact that for the first time in a medical field the inference model considers only the similarity condition of the patients, instead of their features. Our results demonstrate the impressive merits of the proposed medical EGP (MedEGP) method, in comparison to the single GP, and Linear Regression (LR) models to predict the FFR index, with well-calibrated uncertainty.Clinical Relevance- This paper establishes an accurate non-invasive approach to predict the FFR for the diagnosis of coronary artery disease.

[Modern methods of assessment of physiological significance of coronary lesions: A review].

The article describes the main methods of assessment of physiological significance of coronary artery stenoses, their use in clinical practice and future perspectives. New diagnostic methods that are currently under research are discussed.

Invited Commentary: Notwithstanding the Significance of Anatomy in Anomalous Aortic Origin of a Coronary Artery, Physiology Is Important, Too.

The management strategies for anomalous aortic origin of a coronary artery (AAOCA) are based on anatomy, symptoms, and stress tests for evidence of ischemia. These strategies remain associated with low levels of evidence. Stress tests for ischemia or ventricular dysfunction, the only widely used physiological tests, are not adequately reliable. Additional physiological metrics are needed to build reliable strategies. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are physiological measurements that are used in assessing acquired coronary artery disease (CAD). In this commentary, we describe FFR and iFR and review studies supporting their utility in assessing CAD. We describe a few small studies of their use in assessing AAOCA. Finally, we comment on the unique features of AAOCA that mandate further investigation on how to conduct and interpret FFR/iFR measurements. Even at a point where we understand how to do this, determining the effectiveness of these measurements in improving outcomes and guiding management will require lengthy and challenging trials. A collective effort of institutions that manage AAOCA will be essential.

The Impact of Age on the Physiological Assessment of Borderline Coronary Stenoses.

Background and Objectives: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. Materials and Methods: Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. Results: Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. Conclusions: Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.

Diagnostic performance of resting full-cycle ratio in identifying coronary lesions causing myocardial ischaemia: a meta-analysis.

BACKGROUND: The resting full-cycle ratio (RFR), a new non-congestive resting index, is commonly used for physiological evaluations of coronary arteries. AIMS: This study aims to evaluate the accuracy of RFR in detecting coronary artery stenosis with hemodynamic significance using fractional flow reserve (FFR) as the reference standard. METHODS: Using 'RFR, resting full-cycle ratio' as the search term, we searched PubMed, Embase, Cochrane Library, and Web of Science databases, screening the literature according to the inclusion and exclusion criteria. By applying FFR ≤ 0.80 and RFR ≤ 0.89 as the diagnostic criteria for ischaemia, we analysed the synthetic sensitivity, specificity, and corresponding 95% confidence intervals, then synthesised the summary receiver operating characteristic curve (SROC). RESULTS: Three studies were included in this meta-analysis, comprising 1,084 patients with 1,312 lesions. When we used FFR ≤ 0.80 as the reference standard, the synthesised sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of RFR in the diagnosis of coronary ischaemia were 73%, 81%, 67%, 85%, 3.95, and 0.33, respectively. Besides, the area under the curve (AUC) was 0.8276. CONCLUSION: Using FFR as the reference standard, RFR has good diagnostic accuracy in detecting coronary ischaemic lesions and may be an effective alternative to FFR in the future, to some extent.

Serum­derived exosomal hsa­let­7b­5p as a biomarker for predicting the severity of coronary stenosis in patients with coronary heart disease and hyperglycemia.

Exosomal microRNAs (miRNAs/miRs) are potential biomarkers for the diagnosis and treatment of cardiovascular disease, and hyperglycemia serves an important role in the development of atherosclerosis. The present study aimed to investigate the expression profile of serum­derived exosomal miRNAs in coronary heart disease (CHD) with hyperglycemia, and to identify effective biomarkers for predicting coronary artery lesions. Serum samples were collected from eight patients with CHD and hyperglycemia and eight patients with CHD and normoglycemia, exosomes were isolated and differentially expressed miRNAs (DEMIs) were filtered using a human miRNA microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using standard enrichment computational methods for the target genes of DEMIs. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the values of the selected DEMIs in predicting the severity of coronary stenosis. A total of 10 DEMIs, including four upregulated miRNAs (hsa­let­7b­5p, hsa­miR­4313, hsa­miR­4665­3p and hsa­miR­940) and six downregulated miRNAs (hsa­miR­4459, hsa­miR­4687­3p, hsa­miR­6087, hsa­miR­6089, hsa­miR­6740­5p and hsa­miR­6800­5p), were screened in patients with CHD and hyperglycemia. GO analysis showed that the 'cellular process', 'single­organism process' and 'biological regulation' were significantly enriched. KEGG pathway analysis revealed that the 'mTOR signaling pathway', 'FoxO signaling pathway' and 'neurotrophin signaling pathway' were significantly enriched. Among these DEMIs, only hsa­let­7b­5p expression was positively correlated with both hemoglobin A1C levels and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. ROC curves showed that hsa­let­7b­5p could serve as an effective biomarker for differentiating the severity of coronary stenosis. In conclusion, the present study demonstrated that serum­derived exosomal hsa­let­7b­5p is upregulated in patients with CHD and hyperglycemia, and may serve as a noninvasive biomarker for the severity of coronary stenosis.

The importance of baseline fractional flow reserve to detect significant coronary artery stenosis in different patient populations.

INTRODUCTION: Fractional flow reserve (FFR) assessment compares the blood flow on either side of a blockage in the coronary artery and indicates how severe the stenosis is in the artery. Intravenous adenosine is widely used to achieve conditions of stable hyperaemia for the measurement of FR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Therefore, FFR has some limitations, such as the side effects of adenosine and the long procedure time. In addition, there are not enough studies on the evaluation of the baseline ratio of distal coronary pressure to aortic pressure (Pd/Pa) according to standard cut-off values in coronary stenosis under special clinical conditions. This study aimed to assess the diagnostic power of the baseline FFR value for critical coronary stenosis and to determine its predictive value in special patient groups. METHODS: This retrospective study included 158 patients, who were stratified as Q1 (< 0.89), Q2 (0.89-0.92), Q3 (0.93-0.95) and Q4 (> 0.95) based on baseline FFR values. The baseline Pd/Pa value, the change in adenosine FFR and the raw FFR change were recorded. Its predictive value was also calculated for specific patient groups. RESULTS: The threshold value of baseline FFR level for predicting critical stenosis was ≤ 0.92 with a sensitivity of 92.8% and a specificity of 82% (upper limit of Q2 cartilage). Patients with a baseline FFR value ≤ 0.92 had a 58.4-fold greater likelihood of a critical outcome compared with patients with a baseline FFR value > 0.92 (OR: 58.4; 95% CI: 20.3-124.6). In patients with a baseline FFR ≤ 0.92, the Q1 group had a 10.23-fold higher odds of critical stenosis compared with the Q2 group (OR: 10.23; 95% CI: 2.14-48.84). The same values had similar diagnostic power for all specific patient groups. CONCLUSION: The baseline FFR value could be used to predict critical coronary stenosis in our patients and had similar value for predicting lesion severity in all the subgroups.

Invasive physiologic assessment of coronary artery stenosis by resting full-cycle ratio and fractional flow reserve: a prospective observational study.

Resting full-cycle ratio (RFR), an alternative to fractional flow reserve (FFR) for evaluating intermediate coronary artery stenosis, helps reduce patients' time, cost, and discomfort. However, the validation data for RFR and FFR are lacking. We aimed to assess the diagnostic accuracy of RFR and FFR and evaluate effective decision-making for revascularization using their values. Patients subjected to an invasive physiological study for intermediate coronary artery stenosis in Yongin Severance hospital between October 2020 and April 2022 were prospectively and consecutively recruited. We evaluated the correlation between RFR and FFR measurements and the diagnostic performance of RFR (≤ 0.89) versus FFR (≤ 0.80). In all, 474 intermediate coronary stenosis lesions from 400 patients were evaluated using RFR and FFR values. There was a strong linear relationship between RFR and FFR (r = 0.75, 95% CI 0.70-0.78, p < 0.01). Comparing diagnostic performance between RFR and FFR, RFR demonstrated diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 85.0%, 80.0%, 86.7%, 67.1%, and 92.7%, respectively. We analyzed the RFR value in the hyperemia zone (0.86-0.93) according to positive (RFR: 0.86-0.89) and negative (RFR: 0.90-0.93) areas. PPV in positive area is 47.8% (95% Confidence Interval [CI]: 33.8% to 62.0%) and NPV in negative area is 87.7% (95% CI: 80.3% to 93.1%). Excellent correlation exists between RFR and FFR and the diagnostic value of RFR without hyperemia compared with FFR in establishing the accurate functional significance of coronary artery stenosis was shown. RFR alone could evaluate the functional significance of coronary artery stenosis without unnecessary hyperemia, except in the positive area.Trial registration: URL: http://trialsearch.who.int ; Unique identifier: KCT0005255.

Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR.

BACKGROUND AND AIMS: Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038). METHODS: Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). RESULTS: In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32]. CONCLUSIONS: Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups.